Chronic Heart Research Articles

THE RELATIONSHIP BETWEEN DYSLIPIDEMIA AND THE RISK OF COVID 19 INFECTION

OBJECTIVE: The recent coronavirus disease 2019 (COVID-19) outbreak has become a worldwide public health problem. Hypertension, diabetes mellitus, obesity, chronic heart and lung diseases increase the risk of development of COVID-19 infection and severe COVID-19 disease. In this study; we aimed to investigate whether hyperlipidemia alone increases the risk of development of COVID-19 infection.MATERIAL AND METHODS: One hundred-thirty four patients who were hospitalized with the diagnosis of COVID-19 and did not have any chronic disease and one hundred-twenty-two healthy controls were included in this study. The average of the lipid values of the patient group in the last 6 months before admission was calculated. Likewise, the average of the lipid parameters of the control group in the last 6 months was taken.RESULTS: There were no differences between two groups with regard to age, gender, and laboratory characteristics. Triglyceride and Low-density lipoprotein cholesterol values were significantly higher and High-density lipoprotein cholesterol levels were significantly lower in the COVID-19 patients compared to the control subjects (p < 0.01).CONCLUSIONS: Although research on the association of dyslipidemia with COVID-19 is still insufficient, our findings show that serum cholesterol levels are significantly associated with the risk of COVID-19 infection.

Incompressible ankle arteries predict increased morbidity and mortality in patients with an elevated ankle brachial index.

Patients with an elevated ankle brachial index (ABI) > 1.3 have a high burden of disease and poorer outcome compared to patients with a lower ABI. Previously differences between patients with ABI > 1.3 have not been studied in detail. The aim of this study was to analyze the morbidity and mortality of patients with ABI > 1.3. ABI measurements were performed in the vascular laboratory of Turku university hospital 2011-2013. Patients with ABI>1.3 in at least one lower limb were included in the study and divided into 3 groups: At least one lower limb ABI 1.3-2.5 but both limbs <2.5 (group 1), one limb ABI ≥2.5 (group 2), both limbs ABI ≥ 2.5 (group 3). 534 patients were included in the study. The patients in groups 2 and 3 were more often female (p < .001), older (p < .001), had more diabetes (p = .013), coronary artery disease (p = .001) and chronic heart (p = .010) and kidney failure (p = .013) compared to patients in group 1. The survival of patients in group 2 and 3 was significantly poorer compared to the patients in group 1 (HR1.6, 95% CI 1.2-2.2, p = .002 and 1.7, 95% CI 1.2-2.3, p < .001, respectively). Overall and cardiovascular mortality was higher in groups 2 and 3 than group 1.39.5% of patients with incompressible ankle arteries (ABI ≥ 2.5) in both lower limbs had toe pressure (TP) <50mmHg and a poorer survival compared to patients with a higher TP. Patients with incompressible ankle arteries have significantly higher overall and cardiovascular mortality and a greater burden of disease compared to the patients with a measurable yet abnormally high ABI. TP is a useful diagnostic tool when ABI is immeasurably high. All patients with ABI > 1.3 should be considered as high cardiovascular risk patients.

Upregulated circulating mir-424 and its' diagnostic value for gram-negative bacteremia after thoracic transplantation.

AimsEarly post-transplant complications such as acute graft rejection and infections are associated with high morbidity and mortality of heart and lung transplant recipients who are in vital need of immunosuppressive therapy. MiR-424 is a member of the miR-16 family, which plays an important physiological role in the development of cardiovascular and respiratory pathology, is involved in the regulation of monocyte and macrophage differentiation, and has an immunosuppressive potential. The aim of the study was to determine the diagnostic value of circulating miR-424 as a potential biomarker of post-transplant complications in heart and lung transplant recipients.MethodsThe study enrolled 83 heart transplant recipients, aged 18 to 70 (48 ± 13) years; 26 lung transplant recipients, aged 10 to 74 (36 ± 16) years. The miR-424 plasma expression was detected by real-time PCR (Qiagen, USA). Significance of miR-424 level was assessed through the ΔCt method. Acute graft rejection was verified by the results of endomyocardial or transbronchial biopsy. Post-transplant infectious complications were verified through microbiological identification of bacteremia from blood cultures.ResultsOur study shows miR-424 upregulation in plasma of patients with chronic heart or respiratory failure in comparison with healthy individuals (p = 0.003 and p = 0.04 resp.). There was a direct correlation of miR-424 expression with red blood cells and hemoglobin levels in patients before heart transplantation (p = 0.01 and p = 0.03 resp.). After transplantation the expression of plasma miR-424 correlated with the level of C-reactive protein (CRP) both in heart (r = 0.75; p = 0.02) and lung (r = 0.50; p = 0.04) transplant recipients. The expression of plasma miR-424 correlated with tacrolimus blood concentration after heart transplantation (r = 0.38; p = 0.04). The miR-424 level didn't differ in heart or lung transplant recipients with and without acute graft rejection (p = 0.47 and p = 0.78 resp.), but was significantly higher in heart and lung transplant recipients with gram-negative bacteremia (p = 0.002). When the miR-424 level is above a threshold value (−5.72 fold change), the relative risk of bacteremia is RR = 3.84 [95% CI 1.94–7.61]; Se = 60.0%; Sp = 89.2%. CRP concentration above 7 mg/L in duplex test with miR-424 improves the diagnostic characteristics of miR-424 for post-transplant gram-negative bacteremia in heart and lung transplant recipients up to RR = 9.17 [95% CI 1.37–61.46]; Se = 83.3% and Sp = 90.1%.ConclusionMiR-424 plasma expression was upregulated in patients with chronic heart and respiratory failure and in heart and lung transplant recipients in the early post-transplant period. The duplex test, including miR-424 and CRP, has a diagnostic value for detecting the high risk of post-transplant gram-negative bacteremia in heart and lung transplant recipients.

Prevalence and predictors of depression, anxiety and stress among frontline healthcare workers at COVID-19 isolation sites in Gaborone, Botswana.

Coronavirus disease 2019 (COVID-19) has been associated with mental health outcomes and healthcare workers (HCWs) are at the highest risk. The aim of this study was to determine the prevalence and predictors of depression, anxiety and stress, among frontline HCWs at COVID-19 isolation and treatment sites in Gaborone, Botswana. This was a cross-sectional study using self-administered questionnaires at the six (6) isolation facilities. The 42-item Depression, Anxiety and Stress Scale (DASS-42) was used to assess for the outcomes. The proportions are presented with 95% confidence intervals (95% CI). Logistic regression analysis identified predictors of the outcomes. A p value of <0.05 was considered significant. A total of 447 participants with a median age of 30 years responded. Depression, anxiety and stress were detected in 94 (21.0% (95% CI 17.3-25.1%)), 126 (28.2% (CI 24.1-32.6%)) and 71 (15.9% (12.6-19.6%)) of the participants respectively. Depression was associated with smoking (AOR 2.39 (95% CI 1.23-4.67)), working at the largest COVID-19 isolation centre, Sir Ketumile Masire Teaching Hospital (SKMTH) (AOR 0.25 (95% CI 0.15-0.43)) and experience of stigma (AOR 1.68 (95% CI 1.01-2.81)). Tertiary education (AOR 1.82 (95% CI 1.07-3.07)), SKMTH (AOR 0.49 (95% CI 0.31-0.77)), household members with chronic lung or heart disease (AOR 2.05 (95% CI 1.20-3.50)) and losing relatives or friends to COVID-19 (AOR 1.72 (95% CI 1.10-2.70)) were predictors of anxiety. Finally, predictors of stress were smoking (AOR 3.20 (95% CI 1.42-7.39)), household members with chronic heart or lung disease (AOR 2.44 (95% CI 1.27-4.69)), losing relatives or friends to COVID-19 (AOR 1.90 (1.05-3.43)) and working at SKMTH (AOR 0.24 (0.12-0.49)). Depression, anxiety and stress are common among frontline HCWs working in the COVID-19 isolation sites in Gaborone. There is an urgent need to address the mental health outcomes associated with COVID-19 including addressing the risk factors identified in this study.

Risk trajectories of complications in over one thousand newly diagnosed individuals with type 2 diabetes

Although the increased risk of complications of type 2 diabetes (T2D) is well known, there is still little information about the long-term development of comorbidities in relation to risk factors. The purpose of the present study was to describe the risk trajectories of T2D complications over time in an observational cohort of newly diagnosed T2D patients, as well as to evaluate the effect of common risk factors on the development of comorbidities. This national cohort study investigated individuals with T2D in the Swedish National Diabetes Register regarding prevalence of comorbidities at the time of diagnosis, and the incidence of cardiovascular disease (CVD), chronic kidney disease (CKD) and heart failure in the entire patient cohort and stratified by HbA1c levels and age at baseline. Multivariable Cox regressions were used to evaluate risk factors predicting outcomes. We included 100,878 individuals newly diagnosed with T2D between 1998 and 2012 in the study, with mean 5.5 years follow-up (max 17 years). The mean age at diagnosis was 62.6 ± SD12.5 years and 42.7% of the patients were women. Prevalent CVD was reported for 17.5% at baseline. Although the prevalence of comorbidities was generally low for individuals 50 years or younger at diagnosis, the cumulative incidence of the investigated comorbidities increased over time. Newly diagnosed CVD was the most common comorbidity. Women were shown to have a lower risk of developing comorbid conditions than men. When following the risk trajectory of comorbidities over a period of up to 15 years in individuals with type 2 diabetes, we found that all comorbidities gradually increased over time. There was no distinct time point when onset suddenly increased.

Pneumococcal vaccination coverage among adults newly diagnosed with underlying medical conditions and regional variation in the U.S.

BackgroundThe Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommends pneumococcal vaccination for adults with chronic or immunocompromising conditions to prevent pneumococcal disease, yet vaccination rates are low and have limited information on regional variation. This study examines factors associated with pneumococcal vaccination in adults with underlying conditions and describes regional variation in vaccination across the U.S. MethodsUsing IBM MarketScan Commercial Database and Medicare Supplemental Database, this retrospective cohort study included adults ages 19–64 newly diagnosed with chronic (i.e. diabetes, chronic heart, lung, or liver disease, alcohol or tobacco dependence) or immunocompromising (i.e. cancer, chronic renal disease, organ transplant, HIV/AIDS, and asplenia) conditions in 2013. Adults were followed up until the time of pneumococcal vaccination, death, or December 31, 2019, whichever came first. Cox proportional hazards model was used to examine factors associated with vaccination. Vaccination rate was calculated by metropolitan statistical area (MSA) and visually represented on a U.S. map. Results255,330 adults were included. Vaccination rate increased from 6.0% to 21.1% among adults with one year and five years of follow-up, respectively. It took 2.4 years on average for adults to receive vaccination after initial diagnosis. Adults ages 50–64, 35–49 (relative to 19–34) or receiving influenza vaccination were more likely to receive pneumococcal vaccinations. Adults with HIV/AIDS were more likely and those with other conditions were less likely to be vaccinated than those with diabetes. Adults being diagnosed by other providers were less likely to be vaccinated than those diagnosed by primary care providers. Vaccination rate varied largely across MSAs, ranging from 0.0% (Ames, IA; Cheyenne, WY) to 34.0% (Ann Arbor, MI). ConclusionPneumococcal vaccination remains low and most adults with underlying conditions are unvaccinated. Insights into factors associated with vaccination, including regional variability, can help to increase pneumococcal vaccination.

New evidence: Cryoballoon ablation vs. antiarrhythmic drugs for first-line therapy of atrial fibrillation.

Atrial fibrillation (AF) is a commonly encountered chronic and progressive heart rhythm disorder, characterized by exacerbations and remissions. Contemporary clinical practice guidelines recommend a trial of antiarrhythmic drugs (AADs) as the initial therapy for sinus rhythm maintenance; however, these medications have modest efficacy and are associated with significant adverse effects. Recently, several trials have demonstrated that an initial treatment strategy of cryoballoon catheter ablation significantly improves arrhythmia outcomes (e.g. freedom atrial tachyarrhythmia and reduction in arrhythmia burden), produces clinically meaningful improvements in patient-reported outcomes (e.g. symptoms and quality of life), and significantly reduces subsequent healthcare resource utilization (e.g. hospitalization), without increasing the risk of serious or any adverse events. These findings are relevant to patients, providers, and healthcare systems, helping inform the decision regarding the initial choice of rhythm-control therapy in patients with treatment-naïve AF.

Association between oxygen saturation level during bronchoscopy and post-bronchoscopy adverse events: a retrospective cohort study

BackgroundFlexible bronchoscopy is widely used to diagnose and treat various respiratory diseases. However, caution is warranted for post-bronchoscopy adverse events. Although desaturation frequently occurs during bronchoscopy, its clinical impact and the optimal oxygen saturation level during the procedure remain unclear. This study aimed to investigate whether the percutaneous oxygen saturation (SpO2) level during bronchoscopy is associated with the development of post-bronchoscopy respiratory adverse events.MethodsIn this single-center retrospective cohort study conducted from March 2020 to February 2021, 569 patients were classified into high or low oxygen saturation groups based on the SpO2 level during bronchoscopy. The primary outcome was post-bronchoscopy respiratory adverse events, and secondary outcomes were other post-bronchoscopy adverse events and clinical outcomes.ResultsAmong 569 patients, 458 and 111 patients were classified into the high oxygen saturation (SpO2 > 96%) and low oxygen saturation (SpO2 ≤ 94%) groups, respectively. After propensity score matching, the low oxygen saturation group had more post-bronchoscopy respiratory and febrile adverse events than the high oxygen saturation group. In the multivariable regression analysis, low SpO2 level during bronchoscopy was an independent risk factor for post-bronchoscopy respiratory adverse events (odds ratio = 3.16 [95% confidence interval 1.37–7.30]). In the low oxygen saturation group, the high-risk subgroups for post-bronchoscopy respiratory adverse events were the elderly, women, current smokers, and patients with chronic obstructive pulmonary disease or acute decompensated heart failure before bronchoscopy. There was no significant difference in the length of hospital stay, intensive care unit admission, or mortality between the high and low oxygen saturation groups.ConclusionsClose monitoring is recommended for patients with SpO2 ≤ 94% during bronchoscopy due to the increased risk of respiratory adverse events after the procedure.

1253-P: Thirty-Day Readmission Rate and Economic Burden among Type 2 Diabetes with Coexisting Chronic Systolic Heart Failure and Atrial Fibrillation

Introduction: We sought to determine the 30-Day Readmission rate (30-DRr) for patients with Type 2 Diabetes (T2DM) with coexisting Chronic Systolic Heart failure (cSHF) and Atrial Fibrillation (AF) , readmission rate mortality, &amp; healthcare utilization in the United States. Methods: Using the 2017-2018 National Readmission Database, we conducted a retrospective analysis of patient discharges with T2DM as a principal diagnosis and cSHF&amp;AF as a secondary diagnosis. Readmission was defined as the first admission for any non-trauma diagnosis within 30 days of the index admission. The outcomes were 30DRr, readmission mortality rate &amp; resource utilization defined by LOS, Average &amp; Total patient charges/hospital costs. Results: A total of 29,967 index hospitalization for T2DM with co-existing cSHF &amp; AF; mean age was 71.4years, &amp; 69.8% males. In-hospital mortality rate for index admission was 2.89%, while 30-DRr was 17.5% (Figure 1) . The In-hospital mortality rate was 6.78% among this group of readmitted patients, compared to index admission (6.78% vs. 2.89%, adjusted p=0.0001) . The total hospital days associated with readmission were 34,691 days, with a total hospital cost burden of $78,400,000 &amp; a total economic burden on patients of $344,000,000. Conclusion: T2DM with cSHF&amp;AF had a high number of 30-DRr, associated with incremental mortality &amp; high health care burden. Disclosure M.Fatuyi: n/a. L.Pereira: None. V.Sharma: None. L.Khokhlov: None. V.Namdarizandi: None. A.Zain elabidin: None. R.T.Orji: None. K.Shemisa: Speaker's Bureau; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, ESPERION Therapeutics, Inc., Merck &amp; Co., Inc., Pfizer Inc.

CENTRAL BLOOD PRESSURE MEASUREMENT IN CHILDREN AND ADOLESCENTS: SYSTEMATIC REVIEW

Objective: Central aortic blood pressure (BP) has attracted the researchers interest due to its potential to improving cardiovascular risk stratification. We reviewed the published data on central BP in children and adolescents excluding those with chronic heart, lung or kidney disease, congenital anomaly or syndrome, malignancy, and acute illness. Design and method: A systematic review of literature based on PubMed database was conducted by two independent researchers up to January 2021 in accordance with the PRISMA guidelines. Additional studies were identified from the reference lists of relevant articles. Results: A total of 56 eligible articles were identified (Table). The available literature advocates a positive association between male gender, age, height, African-American descent, preterm birth, hypertension and diabetes with central BP, whereas the association of birth weight and physical exercise with central BP was inverse. Regarding the relationship of central BP with indices of preclinical target organ damage, 11 studies showed a positive association with pulse wave velocity, 7 with left ventricular mass index, 5 with carotid intima-media thickness, and 4 with augmentation index. Two studies reported an inverse association with the equivalent of the central retinal artery. The studies testing non-invasive techniques for central BP estimation reported that they approach the invasive technique with adequate accuracy, with crucial impact of the calibration method. Tonometry remains the most studied non-invasive measurement method, followed by oscillometry. Two studies provided normalcy values using the oscillometric method. The evidence on 24-hour ambulatory central BP is limited. Conclusions: The evidence on central BP measurement in youth is limited and derived from non-invasive evaluation in static conditions using tonometry. Central BP in children and adolescents seems to be affected by multiple factors and is associated with preclinical target organ damage.

Outcomes of cardiac tamponade in patients with lung cancer.

e21083 Background: Cardiac tamponade is a serious complication of pericardial effusion and life-threatening cardio-oncological emergency. The prevalence of malignant pericardial effusion varies between 1% and 20% in autopsy studies. Primary lung cancer is the most common cause of metastatic tumor involving the pericardium. The common triggers for pericardial effusion in patients with lung cancer include cancer itself, chemotherapy and radiation therapy. The outcomes of cardiac tamponade in patients with lung cancer remain to be elucidated. Methods: We conducted a retrospective analysis of the 2016 to 2018 Nationwide Inpatient Sample. Adult patients with lung cancer and cardiac tamponade (age ≥ 18) were selected using the ICD-10 diagnosis code. Discharge-level weight analysis was used to produce a national estimate. A univariate and multivariable hierarchical regression analysis was performed to calculate the odds ratio (OR). Results: During the study period, 1,207,580 patients were admitted due to lung cancer of which 7,105 (0.6%) developed cardiac tamponade. Patients with cardiac tamponade tended to be younger (63.2 SE 0.3 vs 69.1 SE 0.2), male (54.5% vs 51.2%) and large proportion of radiation treatment (0.9% vs 0.7%), and smaller proportion of diabetes (18.5% vs 24.2%), chronic kidney disease (4.5% vs 7.6%) and heart failure (15.9% vs 16.2%). After adjusting for age, sex, comorbidity burden and heart failure, cardiac tamponade increased the risk for in-hospital mortality (OR 2.1; 1.9 – 2.5; p &lt; 0.001), major adverse cardiac events (OR 1.6; 1.3 – 2.1; p &lt; 0.001) and acute respiratory failure (OR 2.3; 2.0 – 2.5; p &lt; 0.001). Furthermore, cardiac tamponade was associated with longer length of stay (8.6 SE 0.2 vs 6.0 SE 0.01, p &lt; 0.001) and higher total hospital cost ($118,708.0 SE $4,027.1 vs $65,369.8 SE $170.6). Conclusions: In conclusion, patients with lung cancer who developed cardiac tamponade were associated with poor outcomes including higher in-hospital mortality, MACE, acute respiratory failure, a longer length of stay by 2.6 days, and higher cost of hospitalization. Cardiac tamponade was more common in males and patients who received radiation therapy. Further studies are warranted to develop an optimal management guideline for this cardio-oncological emergency.

1501-PUB: Pharm2Home Initiative: Pharmacist-Led, Chronic-Disease-and-Medication-Therapy Management between Medical Appointments

Objective: The mission of this initiative is to get to know each participant behind their diagnoses - through telehealth and home visits - for enhancing the personalized healthcare delivery in chronic disease management. The initiative emphasizes on the management of type 2 diabetes (T2D) , hypertension, chronic kidney disease, COPD, heart failure, and asthma. This abstract focuses on evaluating outcomes relating to T2D. Methods: The evaluation uses a cross-sectional design to summarize the baseline demographic data pertaining to participants and analyze outcomes from June to December 2021. Descriptive statistics were used to study the current outcomes of the initiative. Results: The selected process and impact outcomes are summarized along with demographic information. Conclusion: Many participants increased frequencies on blood glucose and pressure monitoring. These behavioral changes are translated into A1c improvement. Through connecting with participants, their urgent medical needs were met when primary care providers (PCPs) were unavailable, e.g., resolving hypoglycemia episodes, medication titrations for managing hyperglycemia. Findings have shown that this model refines the care delivery for patients with diabetes going beyond the walls of clinics by partnering clinical pharmacists with diabetologists and PCPs at a safety-net clinic system. Disclosure C.F.Young: Advisory Panel; Sanofi-Aventis U.S. S.Wong: None. Funding Sutter Health

1240-P: Real-World Demographics and Clinical Characteristics of Type 2 Diabetes Mellitus Patients in Ontario, Canada

Population-based studies of diabetes may be limited by sampling and capture. Our study utilizes the Ontario Diabetes Database, which captures all persons in Ontario, Canada with non-gestational diabetes. Based on sensitive and specific cohort definitions adults with T2DM were identified. Study objectives are to investigate: the demographic and the clinical characteristics of type 2 diabetes patients in Ontario, Canada over a time frame from Apr 1, 2002 to Sept 31, 2017. We also compare the demographics and clinical characteristics of T2DM patient populations from the cohorts to understand the impact T2DM definitions have on characterizing the disease. We identify 1,093,812 and 783,228 in the cohorts (Table 1) . In the sensitive and specific cohorts, the mean age of a patient with T2D is 64 to 65 years old and 52 to 54% are male, respectively. Roughly 56 to 64% of patients have a 1-year mean HbA1c of &amp;lt;7%, with ∼ 25 to 32% at 7.0%-8.5%, respectively. Overall, covariates of interest in our demographics and clinical characteristics analysis are similar for both cohorts. Our results show multiple comorbidities in this population; hypertension (∼ 77-79%) , dyslipidemia (∼55%) , chronic ischemic heart disease (∼28%) and angina (∼21%) . The comorbidities further illustrate a substantial proportion of T2DM patients suffer comorbid heart diseases. Disclosure R.L. Houlden: Advisory Panel; Novo Nordisk Canada Inc. Research Support; AstraZeneca. Speaker's Bureau; Abbott Diagnostics, Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk Canada Inc., Sanofi. S. Golden: Other Relationship; Novo Nordisk Canada Inc. W. Shi: Other Relationship; Novo Nordisk Canada Inc. A.A. Kukaswadia: Other Relationship; Novo Nordisk. A. Sharma: Other Relationship; Novo Nordisk Canada Inc. K. Quansah: Employee; Boehringer Ingelheim (Canada) Ltd., Novo Nordisk Canada Inc. A.R. Liu: Employee; Novo Nordisk A/S, Novo Nordisk Canada Inc.

873-P: Machine-Learning Models to Predict CKD and HF in Type 2 Diabetes Patients

Chronic kidney disease (CKD) and heart failure (HF) are the first and most frequent, and life-threatening comorbidities in type 2 diabetes (T2D) patients. Early intervention is important to prevent CKD and HF onset and to improve prognosis of these patients; however, the risk assessment of CKD and HF remains to be established. We aimed to build a machine learning model to predict the risk of CKD or HF onset in the early-stage T2D patients without a history of CKD or cardiovascular diseases (CVD) . We developed prediction models using light gradient boosting machine (LightGBM) , neural network, logistic regression, and Cox proportional hazards model. The model was derived and validated in a sample of 217,054 T2D patients aged ≥18 years without a history of CKD or CVD extracted from a Japanese hospital-based administrative claims data. The outcomes used for the prediction model were diagnosis of incident CKD or HF and hospitalization for CKD or HF in 1, 2, 3, and 5 years. Based on the importance, 60 characteristics and laboratory data were selected and used for models. LightGBM outperformed other models in all outcomes, with AUROCs 0.777 for diagnosis of incident CKD or HF, and 0.785 for hospitalization for CKD or HF in 5years. (Figure) The present study demonstrated successful development of prediction algorithms to support identifying T2D patients with high-risk of CKD or HF onset, which will contribute to improvement of patient prognosis. Disclosure H. Tsubota: Employee; AstraZeneca. A. Suzuki: Research Support; Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Amgen K.K., Eli Lilly and Company, Novo Nordisk A/S. M. Makino: None. E. Kanda: None. T. Yajima: Employee; AstraZeneca. Y. Kidani: Employee; AstraZeneca. N. Morita: Employee; AstraZeneca.

182-OR: Clinical Effects of SGLT2 Inhibitors in HNF1A-Diabetes (MODY3) : A Case Series

Mutations in hepatocyte nuclear factor 1-alpha (HNF1A) cause HNF1A-diabetes (or maturity-onset diabetes of the young type 3 (MODY3)) . Treatment of HNF1A-diabetes is primarily based on sulphonylureas (SU) and secondarily insulins, glucagon-like peptide 1 receptor agonists (GLP1-RA) and dipeptidyl peptidase-4 inhibitors (DPP4i) . Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are effective glucose-lowering agents, cause body weight loss and protect from chronic kidney disease, heart failure and major adverse cardiovascular events. The utility of SGLT2i in patients with HNF1A-diabetes is unknown. Here, we describe a case series of five patients with HNF1A-diabetes treated with SGLT2i. Patient characteristics (median [range]) : age: 52 [35; 68] years; men/women: n=4/1; diabetes duration: 23 [9; 55] years; age at diabetes onset: 18 [13; 44] years; HbA1c: 6.9 [6.0; 7.4]% (52 [42; 57] mmol/mol) ; body weight: 92.3 [65.5; 95.1] kg; BMI: 25.6 [23.8; 29.4] kg/m2. At baseline, patients were treated with SU (n=5) , insulin (n=3; total daily dose: 15 [6; 25] IE divided into 1-4 injections/day) , DPP-4i (n=3) , GLP1-RA (n=2) , metformin (n=1) . All patients were started on empagliflozin mg QD. Follow-up was 1.5 [0.7; 1.8] years (total 6.2 patient years) . After three to six months of SGLT2i therapy, HbA1c was 6.1 [5.5; 7.5]% (43 [37; 59] mmol/mol) and had decreased in four patients (HbA1c change: -0.5 [-1.3; 0.7]% (-5 [-14; 8] mmol/mol)) , while body weight had decreased in all patients (change: -3.4 [-5.9; -1.5] kg) . During SGLT2i treatment, insulin was fully ceased in two patients and insulin dose was reduced from 15 IE/day to 3 IE/day in one patient. No serious adverse events were reported. Our data suggest that SGLT2i is safe, have glucose-lowering effects and is well-tolerated in HNF1A-diabetes, but randomized controlled trials are needed. Disclosure H.Maagensen: None. S.Haedersdal: None. J.Krogh: None. T.Hansen: None. F.K.Knop: Advisory Panel; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk, Sanofi, ShouTi, Zucara Therapeutics, Consultant; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pharmacosmos A/S, Sanofi, ShouTi, Zealand Pharma A/S, Zucara Therapeutics, Research Support; AstraZeneca, Novo Nordisk, Sanofi, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Stock/Shareholder; Antag Therapeutics. T.Vilsbøll: Consultant; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Gilead Sciences, Inc., GlaxoSmithKline plc., Merck Sharp &amp; Dohme Corp., Mundipharma, Novo Nordisk, Sun Pharmaceutical Industries Ltd.

Long-Term Health Effects of Curative Therapies on Heart, Lungs, and Kidneys for Individuals with Sickle Cell Disease Compared to Those with Hematologic Malignancies.

The goal of curing children and adults with sickle cell disease (SCD) is to maximize benefits and minimize intermediate and long-term adverse outcomes so that individuals can live an average life span with a high quality of life. While greater than 2000 individuals with SCD have been treated with curative therapy, systematic studies have not been performed to evaluate the long-term health effects of hematopoietic stem cell transplant (HSCT) in this population. Individuals with SCD suffer progressive heart, lung, and kidney disease prior to curative therapy. In adults, these sequalae are associated with earlier death. In comparison, individuals who undergo HSCT for cancer are heavily pretreated with chemotherapy, resulting in potential acute and chronic heart, lung, and kidney disease. The long-term health effects on the heart, lung, and kidney for children and adults undergoing HSCT for cancer have been extensively investigated. These studies provide the best available data to extrapolate the possible late health effects after curative therapy for SCD. Future research is needed to evaluate whether HSCT abates, stabilizes, or exacerbates heart, lung, kidney, and other diseases in children and adults with SCD receiving myeloablative and non-myeloablative conditioning regimens for curative therapy.

New-onset COVID-19–related diabetes: an early indicator of multi-organ injury and mortally of SARS-CoV-2 infection

ObjectiveThe pandemic of 2019 coronavirus (SARS-CoV-2) disease (COVID-19) has imposed a severe public health burden worldwide. Most patients with COVID-19 were mild. Severe patients progressed rapidly to critical condition including acute respiratory distress syndrome (ARDS), multi-organ failure and even death. This study aims to find early multi-organ injury indicators and blood glucose for predicting mortality of COVID-19.MethodsFasting blood glucose (FBG) ≥7.0 mmol/L for two times during hospitalization and without a history of diabetes were defined as new-onset COVID-19-related diabetes (CRD). Indicators of injuries for multiple organs, including the lung, heart, kidney and liver, and glucose homeostasis were specifically analyzed for predicting death.ResultsA total of 120 patients with a severity equal to or greater than Moderate were hospitalized. After excluding patients with history of diabetes, chronic heart, kidney, and liver disease, 69 patients were included in the final analysis. Of the 69 patients, 23 were Moderate, 20 were Severe, and 26 were Critical (including 16 deceased patients). Univariable analysis indicated that CRD, lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), creatine kinase (CK) and creatinine (Cr) were associated with death. Multivariable analysis indicated that CRD was an independent predictor for death (HR = 3.75, 95% CI 1.26–11.15). Abnormal glucose homeostasis or CRD occurred earlier than other indicators for predicting poor outcomes. Indicators of multiple organ injury were in parallel with the expression patterns of ACE2 (the SARS-CoV-2 receptor) in different organs including pancreatic islet.ConclusionsNew-onset COVID-19-related diabetes is an early indicator of multi-organ injury and predictor for poor outcomes and death in COVID-19 patients. As it is easy to perform for clinical practices and self-monitoring, glucose testing will be helpful for predicting poor outcomes to facilitate appropriate intensive care.

0700 Prospective and Cross-sectional Associations Between Sleep Apnea and Disease in a Phenome-wide Analysis of a Clinical Biobank

Abstract Introduction The potential contributions of sleep apnea (SA) to the risk of developing many diseases remain unidentified due to survey limits in cohort studies. We aimed to identify novel associations between common comorbidities in participants with SA compared to matched controls in a clinical biobank by leveraging electronic health record (EHR) information informed by natural language processing (NLP)-based phenotyping. We also investigated the relationship between polysomnography (PSG) statistics and these diseases. Methods The sample from the Mass General Brigham Biobank was comprised of 4,876 NLP-defined SA adult cases and 12,314 controls matched on age, biological sex, BMI, race/ethnicity, and healthcare utilization with a “data floor” of minimal EHR information. Prospective (&amp;gt;1 year post SA diagnosis) and cross-sectional analyses considered 527 merged PheCode groups of NLP-defined diseases with ≥1% prevalence. Sex-stratified analyses were also performed. Associations with case/control status were further analyzed using rank-normalized Apnea-hypopnea Index (AHI3p) and the percentage of sleep with hypoxemia &amp;lt;88% (Per88) in 4,544 participants, adjusting for age, biological sex, BMI, and race/ethnicity in a smaller single-night clinic sample (57% with AHI3p ≥15). Results In prospective analyses, 170 diseases had significant odds ratios (OR) when comparing participants with SA versus controls following Bonferroni adjustment (p &amp;lt; 3.3 × 10-5), 8 of which were confirmed using PSG. Lead associations included a broad range of pathophysiology (e.g. chronic pulmonary heart disease, tension headache, and chronic fatigue syndrome). Diseases with higher ORs in women compared to men included chronic pulmonary heart disease, chronic renal failure, congestive heart failure not otherwise specified (NOS), and gout (p for sex interaction ≤3.2 × 10-3). Significant associations with PSG traits included hypertensive heart disease, fluid overload, and heart failure NOS (p ≤7.8 × 10-5). 281 diseases significantly differed in cross-sectional analyses, 41 of which were confirmed using PSG. 37 of these 41 associated diseases had lower p-values for Per88 compared to the AHI3p. Conclusion Sleep apnea may contribute to disease risk across a broad range of pathophysiology, with increased sex-specific risks for multiple common comorbidities. Future work should investigate the specific role of hypoxemia in these associations. Support (If Any) NIH (K01-HL135405, R35-HL135818, U01-HG008685 and P30-AR070253).

Telemedicine diagnosis of acute respiratory tract infection patients is not inferior to face-to-face consultation: a randomized trial.

ABSTRACTObjective To analyze telemedicine diagnostic accuracy in patients with respiratory infections during COVID-19 pandemic compared to face-to-face evaluation in the emergency department.Methods Randomized, unicentric study between September 2020 and November 2020 in patients with any respiratory symptom (exclusion criteria: age >65 years, chronic heart or lung diseases, immunosuppressed). Patients were randomized 1:1 for brief telemedicine followed by face-to-face consultation or direct face-to-face evaluation. The primary endpoint was the International Classification of Diseases code. The secondary analysis comprised length of stay, diagnostic test ordering, medical prescription, and proposed destination.Results Ninety-eight patients were enrolled. The mean age was 36.3±9.7 years old, 57.1% were women, and 81.6% had diagnostic test ordered. Mean grouped by International Classification of Diseases code for upper respiratory tract infection, pharyngotonsillitis, and sinusitis showed no difference between study groups or secondary endpoints. The Telemedicine Group was representative of the population usually evaluated in this center. In the Telemedicine Group (n=48), 18.7% patients would be referred for evaluation at the emergency department. The distribution of diagnoses by telemedicine was 67.4% for upper respiratory tract infection, 2.3% for pharyngotonsillitis, and 0% for sinusitis, being statistically similar to the subsequent face-to-face assessment, respectively: 72.1%, 11.6% and 7% (Kappa 0.386 [95%CI: 0.112-0.66]; p=0.536). Telemedicine ordered COVID-19 molecular (RT-PCR) tests in 76.5% versus 79.4% in face-to-face evaluation (Kappa 0.715 [95%CI: 0.413-1]; p>0.999).Conclusion Diagnostic telemedicine consultation of low-risk patients with acute respiratory symptoms is not inferior to face-to-face evaluation at emergency department. Telemedicine is to be reinforced in the health care system as a strategy for the initial assessment of acute patients. ClinicalTrials.gov Identifier: NCT04806477

Prevalence of multimorbidity and its correlates among older adults in Eastern Nepal

BackgroundThe number of people with multimorbidity is surging around the world. Although multimorbidity has been introduced in policy and practice in developed countries, developing countries like Nepal have not considered it as a matter of public health urgency due to the lack of enough epidemiological data. Multimorbidity profoundly affects older adults’ wellbeing; therefore, it is crucial to estimate its prevalence and determinants. This study aimed to estimate the prevalence of multimorbidity among older adults in Eastern Nepal and identify its correlates.MethodologyA community-based cross-sectional survey was conducted in three districts of Eastern Nepal. Data were collected between July and September 2020, among 847 Nepali older adults, aged 60 and older, where study participants were recruited through a multi-stage cluster sampling technique. Semi-structured interviews were conducted at the community settings to collect data. Logistic regression assessed correlates of multimorbidity. SAS 9.4 was used to run all statistical tests and analyses.ResultsMore than half (66.5%) of the participants had at least one of the five non-communicable chronic conditions; hypertension (31.6%), osteoarthritis (28.6%), chronic respiratory disease (18.0%), diabetes (13.5%), and heart disease (5.3%). The prevalence of multimorbidity was 22.8%. In the adjusted model, increased age (for 70–79 years, OR: 3.11, 95% CI: 1.87–5.18; for 80 + years, OR: 4.19, 95% CI: 2.32–7.57), those without a partner (OR: 1.52, 95% CI: 1.00–2.30), residing in urban areas (OR: 1.71, 95% CI: 1.16–2.51), and distant from health center (OR: 1.66, 95% CI: 1.04–2.64) were significantly associated with multimorbidity.ConclusionsThis study found one in five study participants had multimorbidity. The findings will assist policymakers and stakeholders in understanding the burden of multimorbidity among the older population and identifying the groups in most need of health promotion intervention. Future interventions may include developing horizontal multimorbid approaches and multisectoral strategies specifically tailored to meet the needs of those populations.